Interaction between gut microbiota and immune checkpoint inhibitor-related colitis

Abstract

Immune checkpoint inhibitors (ICIs) have become a promising therapeutic strategy for malignant tumors, improving patient prognosis, along with a spectrum of immune-related adverse events (irAEs), including gastrointestinal toxicity, ICI-related colitis (IRC), and diarrhea. The gut microbiota has been suggested as an important regulator in the pathogenesis of IRC, and microbiota modulations like probiotics and fecal microbiota transplantation have been explored to treat the disease. This review discusses the interaction between the gut microbiota and IRC, focusing on the potential pathogenic mechanisms and promising interventions.

Immune-related adverse events in checkpoint blockade: Observations from human tissue and therapeutic considerations

“…Convincing, if complex, association between the gut microbiome and cancer outcomes in CPI recipients has emerged ( 37 , 38 ). Moreover, case reports have demonstrated faecal microbiota transplant (FMT) can mitigate both anti-PD-1 tumour-resistance and treatment-refractory GI-irAEs ( 39 , 40 ), and antibiotic therapy is correlated with high-grade GI-irAE incidence ( 41 ) – all consistent with a critical immune-mediating role for the microbiome in this setting that has yet to be properly understood ( 42 ).…”

Impact of proton pump inhibitors on the onset of gastrointestinal immune‐related adverse events during immunotherapy

“…More in depth, Firmicutes have been implicated in a higher incidence of irAEs while Bacteroidetes positively correlated with a lower incidence 5 . The GM may therefore directly influence the pathogenesis of irAEs, and indirectly through the regulation of metabolites, cytokines, and immune cells 6 . Moreover, the imbalance of gut‐liver axis caused by GM dysbiosis and/or gut mucosal barrier damage leads to various types of liver diseases, 7 while a higher GM diversity seems to be a protective factor against irAEs 6 .…”

“…5 The GM may therefore directly influence the pathogenesis of irAEs, and indirectly through the regulation of metabolites, cytokines, and immune cells. 6 Moreover, the imbalance of gut-liver axis caused by GM dysbiosis and/or gut mucosal barrier damage leads to various types of liver diseases, 7 while a higher GM diversity seems to be a protective factor against irAEs. 6 Indeed, the concomitant drugs given to these patients may alter GM diversity.…”

“…6 Moreover, the imbalance of gut-liver axis caused by GM dysbiosis and/or gut mucosal barrier damage leads to various types of liver diseases, 7 while a higher GM diversity seems to be a protective factor against irAEs. 6 Indeed, the concomitant drugs given to these patients may alter GM diversity. For example, antibiotics can modify the GM composition, increasing inflammasome signaling, and thus promoting a pro-inflammatory state, susceptible to GI irAEs.…”

Ligilactobacillus salivarius CCFM 1266 modulates gut microbiota and GPR109a-mediated immune suppression to attenuate immune checkpoint blockade-induced colitis

“…Gut microbiota metabolites affect the therapeutic efficacy of ICB therapy as well as the development of ICB-induced colitis. 26 In a clinical study on patients treated with anti-CTLA-4 antibodies from French and Italian cohorts, serum concentrations of short-chain fatty acids were measured, and a correlation was identified between propionate concentrations and shorter progression-free survival. 27 In another report, indole-3-carboxaldehyde, a microbial metabolite of tryptophan, was found to protect mice from ICB-induced colitis by influencing aryl hydrocarbon receptor passage and interfering with the host gut microbial composition.…”